title: Clinical results and pharmacokinetics of sorafenib in chronic hemodialysis patients with metastatic renal cell carcinoma in a single center.
abstract: OBJECTIVE
  We investigated the safety and feasibility of sorafenib in patients with end-stage renal disease undergoing hemodialysis by examining the influence of pharmacokinetic parameters to their benefit and also the occurrence of drug-related adverse events of sorafenib.
  
  
  METHODS
  Ten patients with metastatic renal cell carcinoma undergoing hemodialysis received sorafenib. Initial dose was 200 mg once daily, and the dose was increased up to the maintenance dose of 200 mg twice daily. The pharmacokinetic study was performed after a steady state was reached with 200 mg twice daily in six patients.
  
  
  RESULTS
  Complete response occurred in one patient, partial response in three, stable disease in four and progressive disease in two. Median progression-free survival was 6.3 months. Serious adverse events were found in nine patients, including a Grade 5 subarachnoid hemorrhage and a Grade 4 cerebellar hemorrhage. In the pharmacokinetic study, the geometric mean of maximum concentration and area under the curve from 0 to 10 h of plasma concentration were similar on the day of hemodialysis and the day off hemodialysis. These data were lower than those from Japanese people with healthy kidneys and normal kidney function. There was no association between objective response or the occurrence of serious adverse events and pharmacokinetic parameters.
  
  
  CONCLUSIONS
  Treatment with sorafenib of patients with metastatic renal cell carcinoma undergoing hemodialysis appears to be feasible, but we express some concern about the higher incidence of serious adverse events even with the reduced dose. However, clinical efficacy was not compromised.
authors.affiliation: Department of Urology, Tokyo Women's Medical University, 8-1, Kawada-cho, Shinjuku-ku, Tokyo 162-8666, Japan.
authors.forename: Takafumi
authors.initials: T
authors.lastname: Kennoki
authors.forename: Tsunenori
authors.initials: T
authors.lastname: Kondo
authors.forename: Naoki
authors.initials: N
authors.lastname: Kimata
authors.forename: Jun
authors.initials: J
authors.lastname: Murakami
authors.forename: Isamu
authors.initials: I
authors.lastname: Ishimori
authors.forename: Hayakazu
authors.initials: H
authors.lastname: Nakazawa
authors.forename: Yasunobu
authors.initials: Y
authors.lastname: Hashimoto
authors.forename: Hirohito
authors.initials: H
authors.lastname: Kobayashi
authors.forename: Junpei
authors.initials: J
authors.lastname: Iizuka
authors.forename: Toshio
authors.initials: T
authors.lastname: Takagi
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Yoshida
authors.forename: Kazunari
authors.initials: K
authors.lastname: Tanabe
mesh_terms: D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D001557:Benzenesulfonates / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000556:secondary; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D004921:Erythropoietin / Q000008:administration & dosage; D005240:Feasibility Studies; D006397:Hematinics / Q000008:administration & dosage; D006454:Hemoglobins / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D053208:Kaplan-Meier Estimate; D007676:Kidney Failure, Chronic / Q000209:etiology / Q000628:therapy*; D007680:Kidney Neoplasms / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009536:Niacinamide / Q000031:analogs & derivatives; D010671:Phenylurea Compounds; D047428:Protein Kinase Inhibitors / Q000493:pharmacokinetics / Q000627:therapeutic use; D011725:Pyridines / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D006435:Renal Dialysis; D018401:Sample Size; D000077157:Sorafenib; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D001557:Benzenesulfonates; D006397:Hematinics; D006454:Hemoglobins; D010671:Phenylurea Compounds; D047428:Protein Kinase Inhibitors; D011725:Pyridines; D004921:Erythropoietin; D009536:Niacinamide; D000077157:Sorafenib